title: Lack of tolerance and morphine-induced cross-tolerance to the analgesia of chimeric peptide of Met-enkephalin and FMRFa.
abstract: Chimeric peptide of Met-enkephalin and FMRFa (YGGFMKKKFMRFa-YFa), a kappa-opioid receptor specific peptide, did not induce tolerance and cross-tolerance effects to its analgesic action on day 5 after pretreatment with either YFa or morphine for 4 days. However, pretreatment with YFa for 4 days led to the development of cross-tolerance to the analgesic effects of morphine and also 4 days of pretreatment of morphine resulted in the expression of tolerance to its own analgesic effects. Similar expression of tolerance and cross-tolerance were also observed when YFa was compared with the kappa receptor agonist peptide dynorphin A(1-13) [DynA(1-13)]. Cross-tolerance effects between YFa and DynA(1-13) analgesia were also not observed on day 5. Interestingly, when YFa and DynA(1-13) were tested for their analgesic effects for 5 days, reduction in analgesia on day 3 was observed in case of DynA(1-13) whereas YFa maintained its analgesia for 5 days. Thus, chimeric peptide YFa may serve as a useful probe to understand pain modulation and expression of tolerance and cross-tolerance behavior with other opioids.
authors.affiliation: Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Gupta
authors.forename: Ishwar Dutt
authors.initials: ID
authors.lastname: Vats
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Gupta
authors.forename: Kishwar
authors.initials: K
authors.lastname: Saleem
authors.forename: Santosh
authors.initials: S
authors.lastname: Pasha
mesh_terms: D000698:Analgesia / Q000379:methods; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000235:genetics*; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D011993:Recombinant Fusion Proteins; C509615:YFa peptide, Ser(5)-; D004744:Enkephalin, Methionine; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine